PAULO CESAR COTRIM
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina - Docente
LIM/48 - Laboratório de Imunologia, Hospital das Clínicas, Faculdade de Medicina
LIM/48 - Laboratório de Imunologia, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
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- Hydroxymethylnitrofurazone lymphatic uptake with nanostructured lipid carrier after oral administration in rats(2024) SOUZA, Aline de; SCARIM, Caue Benito; COTRIM, Paulo Cesar; BARBOSA JUNIOR, Fernando; ROCHA, Bruno Alves; CALIXTO, Leandro Augusto; CORREIA, Cristiano Jesus; ARAUJO, Gabriel Lima de Barros; LOBENBERG, Raimar; BOU-CHACRA, Nadia Araci; BREITHAUPT-FALOPPA, Ana CristinaBackground: Leishmaniasis, caused by the protozoan Leishmania sp., infects phagocyte cells present in lymphatic organs. This study demonstrates the influence of nanostructured lipid carrier-loaded hydroxymethylnitrofurazone (NLC-NFOH) on lymphatic uptake using a chylomicron-blocking flow model in rats. Method: Lymphatic uptake of NFOH was assessed 1 h after oral administration of dimethyl sulfoxide with NFOH or NLC-NFOH with and without cycloheximide pretreatment. Result: Dimethyl sulfoxide with NFOH and NLC-NFOH showed NFOH serum concentrations of 0.0316 and 0.0291 mu g/ml, respectively. After chylomicron blocking, NFOH was not detected. Conclusion: Despite log P below 5, NFOH was successfully taken up by the lymphatic system. Long-chain fatty acids and particle size might be main factors in these findings. NLC-NFOH is a promising and convenient platform for treating leishmaniasis via oral administration.
- Targeting Leishmania amazonensis amastigotes through macrophage internalisation of a hydroxymethylnitrofurazone nanostructured polymeric system(2017) MONTEIRO, Lis Marie; LOBENBERG, Raimar; FERREIRA, Elizabeth Igne; COTRIM, Paulo Cesar; KANASHIRO, Edite; ROCHA, Mussya; CHUNG, Man Chin; BOU-CHACRA, NadiaDextran-coated poly (n-butyl cyanoacrylate) nanoparticles (PBCA-NPs) were prepared and were evaluated for enhanced delivery of a promising anti-Leishmania drug candidate, hydroxymethylnitrofurazone (NFOH), to phagocytic cells. Currently available chemotherapy for leishmaniasis, such as pentavalent antimonials, presents low safety and efficacy. Furthermore, widespread drug resistance in leishmaniasis is rapidly emerging. To overcome these drawbacks, the use of nanosized delivery systems can reduce systemic drug toxicity and increase the drug concentration in infected macrophages, therefore improving treatment of leishmaniasis. PBCA-NPs containing NFOH (PBCA-NFOH-NPs) were prepared by an anionic emulsion polymerisation method. The z-average and polydispersity index (PDI) were determined by photon correlation spectroscopy, the zeta potential by microelectrophoresis and the entrapment efficiency by HPLC. Cytotoxicity was determined using macrophages from BALB/c mice. Efficacy tests were performed using Leishmania amazonensis promastigotes and amastigotes. The z-average of PBCA-NFOH-NPs was 151.5 +/- 61.97 nm, with a PDI of 0.104 +/- 0.01, a zeta potential of -10.1 +/- 6.49 mV and an entrapment efficiency of 64.47 +/- 0.43%. Efficacy in amastigotes revealed IC50 values of 0.33 mu M and 31.2 mu M for the nanostructured and free NFOH, respectively (95-fold increase). The cytotoxicity study indicated low toxicity of the PBCA-NFOH-NPs to macrophages. The selectivity index was 370.6, which is 49-fold higher than free NFOH (7.6). Such findings indicated that improved efficacy could be due to NP internalisation following site-specific drug delivery and reactivation of immune protective reactions by the NP components. Thus, PBCA-NFOH-NPs have the potential to significantly improve the treatment of leishmaniasis, with reduced systemic side effects.
- Buparvaquone Nanostructured Lipid Carrier: Development of an Affordable Delivery System for the Treatment of Leishmaniases(2017) MONTEIRO, Lis Marie; LOBENBERG, Raimar; COTRIM, Paulo Cesar; ARAUJO, Gabriel Lima Barros de; BOU-CHACRA, NadiaBuparvaquone (BPQ), a veterinary drug, was formulated as nanostructured lipid carriers (NLC) for leishmaniases treatment. The formulation design addressed poor water solubility of BPQ and lack of human drug delivery system. The DSC/TG and microscopy methods were used for solid lipids screening. Softisan (R) 154 showed highest BPQ solubility in both methods. The BPQ solubility in liquid lipids using HPLC revealed Miglyol (R) 812 as the best option. Response surface methodology (RSM) was used to identify the optimal Softisan154 : Miglyol 812 ratios (7 : 10 to 2 : 1) and Kolliphor (R) P188 and Tween (R) 80 concentration (> 3.0% w/w) aiming for z-average in the range of 100-300 nm for macrophage delivery. The NLC obtained by high-pressure homogenization showed low z-averages (< 350 nm), polydispersity (< 0.3), and encapsulation efficiency close to 100%. DSC/ TG and microscopy in combination proved to be a powerful tool to select the solid lipid. The relationship among the variables, demonstrated by a linear mathematical model using RSM, allowed generating a design space. This design space showed the limits in which changes in the variables influenced the z-average. Therefore, these drug delivery systems have the potential to improve the availability of affordable medicines due to the low cost of raw materials, using well established, reliable, and feasible scale-up technology.
- Co-delivery of buparvaquone and polymyxin B in a nanostructured lipid carrier for leishmaniasis treatment(2019) MONTEIRO, Lis Marie; LOBENBERG, Raimar; FOTAKI, Nikoletta; ARAUJO, Gabriel Lima Barros de; COTRIM, Paulo Cesar; BOU-CHACRA, NadiaObjectives: This study aimed to describe the preparation and in vitro evaluation of a surface-modified nanostructured lipid carrier (NLC) using chitosan and dextran for co-delivery of buparvaquone (BPQ) and polymyxin B (PB) against leishmaniasis. Methods: The NLC was prepared using high-pressure homogenisation. Polymyxin B binding and surface modification with biopolymers were achieved by electrostatic interaction. In vitro cytotoxicity was assessed in mouse peritoneal macrophages, and leishmanicidal activity in amastigotes of Leishmania infantum. Results: The performance attributes of BPQ-NLC, BPQ-NLC-PB[A(-)](anionic) and BPQ-NLC-PB[C+](cationic) were respectively: Z-average 173.9 +/- 1.6, 183.8 +/- 4.5 and 208.8 +/- 2.6 nm; zeta potential -19.6 +/- 1.5, -20.1 +/- 1.1 and 31.1 +/- 0.8 mV; CC50 583.4 +/- 0.10, 203.1 +/- 0.04 and 5.7 +/- 0.06 mu M; IC50 229.0 +/- 0.04, 145.7 +/- 0.04 and 150.5 +/- 0.02 nM. The NLC in vitro leishmanicidal activity showed up to 3.1-fold increase when compared with free BPQ (P < 0.05, alpha = 0.05). Conclusions: The developed NLC proved to be a promising formulation with which to overcome the drawbacks of current leishmaniasis treatment by the co-delivery of two alternative drugs and a macrophage targeting modified surface.